tbuckley/cabot-search huggingface dataset:
Identification and multicentric validation of soluble CDCP1 as a robust serological biomarker for risk stratification of NASH in obese Chinese
Authors: Xi Jia, Erfei Song, Yan Liu, Jiarui Chen, Pei Wan, Yue Hu, Dewei Ye, Subrata Chakrabarti, Hema Mahajan, Jacob George, Sen Yan, Yongtao Yu, Guanghui Zhang, Yong Wang, Wah Yang, Lihong Wu, Shuang Hua, Chi Ho Lee, Huixin Li, Xue Jiang, Karen S.L. Lam, Cunchuan Wang, Aimin Xu
Journal: Cell Reports Medicine (2023)

The definitive diagnosis of non-alcoholic steatohepatitis (NASH) currently relies on invasive and labor-intensive liver biopsy. Here, we identified soluble CUB domain-containing protein 1 (sCDCP1) as a top-ranked non-invasive biomarker for NASH using Olink-based proteomics in 238 obese individuals with liver biopsies. Both the circulating concentration and hepatic mRNA abundance of sCDCP1 were significantly elevated in patients with NASH and correlated closely with each histological feature of NASH. In the pooled multicenter validation cohort, sCDCP1 as a standalone biomarker achieved an area under the receiver operating characteristic (AUROC) of 0.838 (95% confidence interval [CI] 0.789–0.887) for diagnosing NASH, which is better than those achieved with cytokeratin-18 and other non-invasive tests. Furthermore, the C-DAG model established by the combination of sCDCP1 with diabetes, aspartate aminotransferase (AST), and gender accurately rules in and rules out both NASH and fibrotic NASH (gray zones <20%). Thus, sCDCP1-based non-invasive tests can be potentially implemented for screening and early diagnosis of NASH and for ruling out low-risk individuals to avoid unnecessary liver biopsies.
Lung cancer diagnosis and mortality beyond 15 years since quit in individuals with a 20+ pack‐year history: A systematic review
Authors: Karli K. Kondo, Basmah Rahman, Chelsea K. Ayers, Rose Relevo, Jessica C. Griffin, Michael T. Halpern
Journal: CA A Cancer Journal for Clinicians (2023)

Abstract Current US lung cancer screening recommendations limit eligibility to adults with a pack‐year (PY) history of ≥20 years and the first 15 years since quit (YSQ). The authors conducted a systematic review to better understand lung cancer incidence, risk and mortality among otherwise eligible individuals in this population beyond 15 YSQ. The PubMed and Scopus databases were searched through February 14, 2023, and relevant articles were searched by hand. Included studies examined the relationship between adults with both a ≥20‐PY history and ≥15 YSQ and lung cancer diagnosis, mortality, and screening ineligibility. One investigator abstracted data and a second confirmed. Two investigators independently assessed study quality and certainty of evidence (COE) and resolved discordance through consensus. From 2636 titles, 22 studies in 26 articles were included. Three studies provided low COE of elevated lung cancer incidence beyond 15 YSQ, as compared with people who never smoked, and six studies provided moderate COE that the risk of a lung cancer diagnosis after 15 YSQ declines gradually, but with no clinically significant difference just before and after 15 YSQ. Studies examining lung cancer‐related disparities suggest that outcomes after 15 YSQ were similar between African American/Black and White participants; increasing YSQ would expand eligibility for African American/Black individuals, but for a significantly larger proportion of White individuals. The authors observed that the risk of lung cancer not only persists beyond 15 YSQ but that, compared with individuals who never smoked, the risk may remain significantly elevated for 2 or 3 decades. Future research of nationally representative samples with consistent reporting across studies is needed, as are better data from which to examine the effects on health disparities across different populations.
Global Air Pollutant Phenanthrene and Arrhythmic Outcomes in a Mouse Model
Authors: Sana Yaar, Tatiana S. Filatova, Ellie England, Shiva N. Kompella, Jules C. Hancox, David A. Bechtold, Luigi Venetucci, Denis V. Abramochkin, Holly A. Shiels
Journal: Environmental Health Perspectives (2023)

Background: The three-ringed polycyclic aromatic hydrocarbon (PAH) phenanthrene (Phe) has been implicated in the cardiotoxicity of petroleum-based pollution in aquatic systems, where it disrupts the contractile and electrical function of the fish heart. Phe is also found adsorbed to particulate matter and in the gas phase of air pollution, but to date, no studies have investigated the impact of Phe on mammalian cardiac function. Objectives: Our objectives were to determine the arrhythmogenic potential of acute Phe exposure on mammalian cardiac function and define the underlying mechanisms to provide insight into the toxicity risk to humans. Methods: Ex vivo Langendorff-perfused mouse hearts were used to test the arrhythmogenic potential of Phe on myocardial function, and voltage- and current-clamp recordings were used to define underlying cellular mechanisms in isolated cardiomyocytes. Results: Mouse hearts exposed to ∼8μM Phe for 15-min exhibited a significantly slower heart rate (p=0.0006, N=10 hearts), a prolonged PR interval (p=0.036, N=8 hearts), and a slower conduction velocity (p=0.0143, N=7 hearts). Whole-cell recordings from isolated cardiomyocytes revealed action potential (AP) duration prolongation (at 80% repolarization; p=0.0408, n=9 cells) and inhibition of key murine repolarizing currents—transient outward potassium current (Ito) and ultrarapid potassium current (IKur)—following Phe exposure. A significant reduction in AP upstroke velocity (p=0.0445, n=9 cells) and inhibition of the fast sodium current (INa; p=0.001, n=8 cells) and calcium current (ICa; p=0.0001) were also observed, explaining the slowed conduction velocity in intact hearts. Finally, acute exposure to ∼8μM Phe significantly increased susceptibility to arrhythmias (p=0.0455, N=9 hearts). Discussion: To the best of our knowledge, this is the first evidence of direct inhibitory effects of Phe on mammalian cardiac electrical activity at both the whole-heart and cell levels. This electrical dysfunction manifested as an increase in arrhythmia susceptibility due to impairment of both conduction and repolarization. Similar effects in humans could have serious health consequences, warranting greater regulatory attention and toxicological investigation into this ubiquitous PAH pollutant generated from fossil-fuel combustion. https://doi.org/10.1289/EHP12775
Correction: PP2A inhibition overcomes acquired resistance to HER2 targeted therapy
Authors: Martina S. J. McDermott, Brigid C. Browne, Neil T. Conlon, Neil A. O’Brien, Dennis J. Slamon, Michael Henry, Paula Meleady, Martin Clynes, Paul Dowling, John Crown, Norma O’Donovan
Journal: Molecular Cancer (2023)
First US Domestic Case of Concerning Multidrug-Resistant <i>P aeruginosa</i>
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
IL-4 shapes microglia-dependent pruning of the cerebellum during postnatal development
Authors: Joana R. Guedes, Pedro A. Ferreira, Jéssica Costa, Mariana Laranjo, Maria J. Pinto, Tiago Reis, Ana Maria Cardoso, Carolina Lebre, Maria Casquinha, Marcos Gomes, Viktoriya Shkatova, Marta Pereira, Nuno Beltrão, Nicholas Hanuscheck, Andrew D. Greenhalgh, Christina Francisca Vogelaar, Ana Luísa Carvalho, Frauke Zipp, Ana Luísa Cardoso, João Peça
Journal: Neuron (2023)

Interleukin-4 (IL-4) is a type 2 cytokine with pleiotropic functions in adaptive immunity, allergies, and cognitive processes. Here, we show that low levels of IL-4 in the early postnatal stage delineate a critical period in which microglia extensively prune cerebellar neurons. Elevating the levels of this cytokine via peripheral injection, or using a mouse model of allergic asthma, leads to defective pruning, permanent increase in cerebellar granule cells, and circuit alterations. These animals also show a hyperkinetic and impulsive-like phenotype, reminiscent of attention-deficit hyperactivity disorder (ADHD). These alterations are blocked in Il4rαfl/fl::Cx3cr1-CreER mice, which are deficient in IL-4 receptor signaling in microglia. These findings demonstrate a previously unknown role for IL-4 during a neuroimmune critical period of cerebellar maturation and provide a first putative mechanism for the comorbidity between allergic disease and ADHD observed in humans.
PhotoPyro‐Induced cGAS‐STING Pathway Activation Enhanced Anti‐Melanoma Immunotherapy via a Manganese‐Coordinated Nanomedicine
Authors: Yuzhao Feng, Guohao Wang, Wenxi Li, Jie Yan, Xinying Yu, Hao Tian, Bei Li, Yunlu Dai
Journal: Advanced Healthcare Materials (2023)

Malignant melanoma is an aggressive skin cancer with a high metastatic and mortality rate. Owing to genetic alterations, melanoma cells are resistant to apoptosis induction, which reduces the efficacy of most adjuvant systemic anticancer treatments in clinical. Here, a noninvasive strategy for anti-melanoma immunotherapy based on a manganese-coordinated nanomedicine is provided. Supplemented with photoirradiation, photon-mediated reactive oxygen species generation by photosensitizer chlorin e6 initiates photon-controlled pyroptosis activation (PhotoPyro) and promotes antitumor immunity. Simultaneously, photoirradiation-triggered double-stranded DNA generation in the cytosol would activate the Mn
Highlighted research articles
Journal: Cancer Discovery (2023)

In This Issue| November 01 2023 Highlighted research articles Author & Article Information Online ISSN: 2159-8290 Print ISSN: 2159-8274 ©2023 American Association for Cancer Research2023American Association for Cancer Research Cancer Discov (2023) 13 (11): 2293–2294. https://doi.org/10.1158/2159-8290.CD-13-11-ITI Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record November 1 2023 Citation Highlighted research articles. Cancer Discov 1 November 2023; 13 (11): 2293–2294. https://doi.org/10.1158/2159-8290.CD-13-11-ITI Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search Deaths from endometrial cancer (EC) are rising in the United States, with the highest mortality rates reported for Black patients. Weigelt, Marra, and colleagues evaluated 1,882 ECs subjected to clinical tumor–normal panel sequencing, and found high-risk histologic types, including serous carcinoma and carcinosarcoma, and ECs of the poor outcome–related copy number–high/TP53 abnormal molecular subtype to be more prevalent in self-identified Black patients/patients of African genetic ancestry. Lower rates of actionable alterations that confer benefit from immunotherapy were observed in ECs from Black compared to White patients. Together, these findings on the molecular features underpinning EC disparities emphasize the importance of increasing research and clinical trials in high-risk ECs. See article, p. 2356. Effective therapies are lacking for patients with H3K27M-mutant diffuse midline glioma (DMG). Venneti, Kawakibi, Ji, Waszak, Sweha, Mota, Pun, and colleagues reported on the clinical results of ONC201 in patients with H3K27M-DMG from two completed clinical... You do not currently have access to this content.
Correction: Hypoxia Induces Phenotypic Plasticity and Therapy Resistance in Melanoma via the Tyrosine Kinase Receptors ROR1 and ROR2
Journal: Cancer Discovery (2023)

In Fig. 3C in the original version of this article (1), the same image was inadvertently used for the ROR1_5 siRNA-treated and the ROR1_6 + ROR2_5 siRNA-treated 3D spheroids derived from WM35 cells.The figure has been corrected in the latest online HTML and PDF versions of the article.The Fig. 1E legend has also been updated to clarify that the middle and left DAPI stains are the same in the melanocyte panels and the MET-1205Lu panels because these samples were costained with DAPI, ROR2, and Wnt5A.The authors regret the error and omission.
Early Clinical Success of MTA-Cooperative PRMT5 Inhibitors for the Treatment of <i>CDKN2A/MTAP</i>-Deleted Cancers
Authors: Kathleen M. Mulvaney
Journal: Cancer Discovery (2023)

Summary: CDKN2A encodes the tumor suppressors p16 and p14ARF and is the most common homozygously deleted gene in all human cancers; tumors frequently codelete the nearby gene MTAP, creating a dependency on PRMT5. In this issue of Cancer Discovery, Engstrom and colleagues report an MTA-cooperative PRMT5 methyltransferase inhibitor MRTX1719 that selectively kills CDKN2A/MTAP-codeleted cancers and demonstrates early efficacy in clinical trials for solid tumors harboring the CDKN2A/MTAP codeletion. See related article by Engstrom et al., p. 2412 (1).
Highlighted research articles
Journal: Blood Cancer Discovery (2023)

In This Issue| November 01 2023 Highlighted research articles Author & Article Information Online ISSN: 2643-3249 Print ISSN: 2643-3230 ©2023 American Association for Cancer Research2023American Association for Cancer Research Blood Cancer Discov (2023) 4 (6): 419. https://doi.org/10.1158/2643-3230.BCD-4-6-ITI Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record November 1 2023 Citation Highlighted research articles. Blood Cancer Discov 1 November 2023; 4 (6): 419. https://doi.org/10.1158/2643-3230.BCD-4-6-ITI Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search Anti-BCMA bispecific T-cell engager antibodies (BiTE) have demonstrated impressive efficacy in heavily relapsed multiple myeloma patients; however, infections remain a serious concern with these therapies. In this article, Lancman et al. demonstrate that profound and prolonged hypogammaglobulinemia is universal in patients responding to therapy and is a significant driver of infections. Intravenous immunoglobulin (IVIg) replacement mitigates the risk of serious infections ten-fold. The findings support IVIg as a primary prophylaxis throughout the duration of therapy and raise questions about the optimal schedule and duration of BiTE treatment. See article, p. 440. The combination of azacytidine with venetoclax has become the standard first-line treatment for patients with acute myeloid leukemia (AML) unable to tolerate chemotherapy. However, there is still unmet need for not only identifying poor-responding patients but also identifying effective therapeutic strategies for them. In this precision medicine proof-of-concept study, Eide, Kurtz et al. implement ex vivo screening of... You do not currently have access to this content.
Selected Articles from This Issue
Journal: Clinical Cancer Research (2023)

Highlights| November 01 2023 Selected Articles from This Issue Author & Article Information Online ISSN: 1557-3265 Print ISSN: 1078-0432 ©2023 American Association for Cancer Research2023American Association for Cancer Research Clin Cancer Res (2023) 29 (21): 4315. https://doi.org/10.1158/1078-0432.CCR-29-21-HI Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record November 1 2023 Citation Selected Articles from This Issue. Clin Cancer Res 1 November 2023; 29 (21): 4315. https://doi.org/10.1158/1078-0432.CCR-29-21-HI Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search Although combination therapies have improved outcomes in rhabdomyosarcoma (RMS) patients, prognosis remains poor for those who relapse, emphasizing a need for new targeted therapies. The multi-tyrosine kinase inhibitor (TKI) regorafenib targets several kinases associated with RMS, including VEGFR, FGFR, and PDGFR, and has demonstrated promising preclinical antitumor activity in Ewing sarcoma (EWS), neuroblastoma, and RMS models. In this phase I trial, Casanova and colleagues establish a maximum tolerated dose for regorafenib and evaluate the efficacy of regorafenib combined with vincristine and irinotecan in pediatric patients with recurrent/refractory RMS, EWS, neuroblastoma, and Wilms tumor. Treatment was well tolerated, with less than 20% of patients experiencing grade 3/4 adverse events. The authors report an overall response rate of 48% and a disease control rate of 86%, with 2 of 21 of patients achieving complete response, 8 patients demonstrating partial response, and 7 patients maintaining stable disease. Median progression-free survival was 7.0 months,... You do not currently have access to this content.
Ciprofloxacin‐Loaded, pH‐Responsive PAMAM‐Megamers Functionalized with S‐Nitrosylated Hyaluronic Acid Support Infected Wound Healing in Mice without Inducing Antibiotic Resistance
Authors: Guimei Jiang, Renfei Wu, Sidi Liu, Tianrong Yu, Yijin Ren, Henk J. Busscher, Henny C. van der Mei, Jian Liu
Journal: Advanced Healthcare Materials (2023)

Abstract Antimicrobial‐resistant bacterial infections threaten to become the number one cause of death by the year 2050. Since the speed at which antimicrobial‐resistance develops is exceeding the pace at which new antimicrobials come to the market, this threat cannot be countered by making more, new and stronger antimicrobials. Promising new antimicrobials should not only kill antimicrobial‐resistant bacteria, but also prevent development of new bacterial resistance mechanisms in strains still susceptible. Here, PAMAM‐dendrimers are clustered using glutaraldehyde to form megamers that are core‐loaded with ciprofloxacin and functionalized with HA‐SNO. Megamers are enzymatically disintegrated in an acidic pH, as in infectious biofilms, yielding release of ciprofloxacin and NO‐generation by HA‐SNO. NO‐generation does not contribute to the killing of planktonic Gram‐positive Staphylococcus aureus and Gram‐negative Pseudomonas aeruginosa , but in a biofilm‐mode of growth short‐lived NO‐assisted killing of both ciprofloxacin‐susceptible and ciprofloxacin‐resistant bacterial strains by the ciprofloxacin released. Repeated sub‐culturing of ciprofloxacin‐susceptible bacteria in presence of ciprofloxacin‐loaded and HA‐SNO functionalized PAMAM‐megamers does not result in ciprofloxacin‐resistant variants as does repeated culturing in presence of ciprofloxacin. Healing of wounds infected by a ciprofloxacin‐resistant S. aureus variant treated with ciprofloxacin‐loaded, HA‐SNO functionalized megamers proceed faster through NO‐assisted ciprofloxacin killing of infecting bacteria and stimulation of angiogenesis.
The COVID-19 Pandemic: A Special Challenge for the Journal's Editors
Authors: Andreas Kronbichler, L. Parker Gregg, Joanne M. Bargman
Journal: Journal of the American Society of Nephrology (2023)

1Department of Internal Medicine IV, Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria 2Section of Nephrology, Department of Medicine, Selzman Institute for Kidney Health, Baylor College of Medicine, Houston, Texas 3Division of Nephrology, Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas 4Veterans Affairs Health Services Research and Development Center for Innovations in Quality, Effectiveness and Safety, Houston, Texas 5Division of Nephrology, Department of Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada Correspondence: Prof. Andreas Kronbichler, Department of Internal Medicine IV, Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, 6020, Austria. Email: [email protected] A.K. and L.P.G, contributed equally to this work.
A metagenomic analysis for combination therapy of multiple classes of antibiotics on the prevention of the spread of antibiotic-resistant genes
Authors: Matthew Igo, Lei Xu, Ashok Krishna, Sharron Stewart, Lin Xu, Zhihua Li, James L. Weaver, Heather Stone, Leonard Sacks, Timothy Bensman, Jeffry Florian, Rodney Rouse, Xiaomei Han
Journal: Gut Microbes (2023)

Antibiotics used systemically to treat infections may have off-target effects on the gut microbiome, potentially resulting in the emergence of drug-resistant bacteria or selection of pathogenic species. These organisms may present a risk to the host and spread to the environment with a risk of transmission in the community. To investigate the risk of emergent antibiotic resistance in the gut microbiome following systemic treatment with antibiotics, this metagenomic analysis project used next-generation sequencing, a custom-built metagenomics pipeline, and differential abundance analysis to study the effect of antibiotics (ampicillin, ciprofloxacin, and fosfomycin) in monotherapy and different combinations at high and low doses, to determine the effect on resistome and taxonomic composition in the gut of Balb/c mice. The results showed that low-dose monotherapy treatments showed little change in microbiome composition but did show an increase in expression of many antibiotic-resistant genes (ARGs) posttreatment. Dual combination treatments allowed the emergence of some conditionally pathogenic bacteria and some increase in the abundance of ARGs despite a general decrease in microbiota diversity. Triple combination treatment was the most successful in inhibiting emergence of relevant opportunistic pathogens and completely suppressed all ARGs after 72 h of treatment. The relative abundances of mobile genetic elements that can enhance transmission of antibiotic resistance either decreased or remained the same for combination therapy while increasing for low-dose monotherapy. Combination therapy prevented the emergence of ARGs and decreased bacterial diversity, while low-dose monotherapy treatment increased ARGs and did not greatly change bacterial diversity.